Rapid-Acting Treatments for Postpartum Depression: From Neurosteroids to Clinical Implementation: A Narrative Review

Postpartum depression (PPD) is a common and disabling psychiatric condition with significant consequences for maternal functioning, infant development, and family well-being. Although psychotherapy and selective serotonin reuptake inhibitors (SSRIs) remain first-line treatments, their delayed onset of action limits effectiveness in individuals with moderate-to-severe illness, suicidality or marked functional impairment. Over the past decade, advances in perinatal neurobiology have led to the development of rapid-acting interventions targeting gamma-aminobutyric acid (GABA)-A receptor modulation, most notably neuroactive steroids. Brexanolone is an intravenous formulation of allopregnanolone. It showed rapid antidepressant effects but required prolonged monitored infusion and presents substantial implementation challenges. More recently, zuranolone which is an oral neuroactive steroid administered over 14 days has expanded access to rapid-acting treatment while introducing safety considerations related to sedation, driving impairment and lactation counseling. In parallel, electroconvulsive therapy (ECT) remains the most established rapid-acting intervention for severe postpartum mood disorders while repetitive transcranial magnetic stimulation (rTMS) and ketamine-based approaches continue to evolve. This narrative review synthesizes the historical development, mechanistic rationale, clinical evidence, and real-world implementation considerations for rapid-acting treatments in PPD, emphasizing patient selection, safety monitoring, breastfeeding considerations, and integration into multidisciplinary perinatal care pathways to optimize outcomes and equity of access.